Research Original Investigation
Warfarin Interactions With Antibiotics
16. Mahé I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621-1627.
19. Dowd MB, Vavra KA, Witt DM, Delate T, Martinez K. Empiric warfarin dose adjustment with prednisone therapy: a randomized, controlled trial. J Thromb Thrombolysis. 2011;31(4):472-477.
17. Hirsh J, Fuster V, Ansell J, Halperin JL; American Heart Association; American College of Cardiology Foundation. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation. 2003;107(12):1692-1711.
20. Ahmed A, Stephens JC, Kaus CA, Fay WP. Impact of preemptive warfarin dose reduction on anticoagulation after initiation of trimethoprim-sulfamethoxazole or levofloxacin. J Thromb Thrombolysis. 2008;26(1):44-48.
18. Richards RK. Influence of fever upon the action of 3,3methylene bis-(4-hydroxycoumarin) (dicumarol). Science. 1943;97(2518):313-316.
21. Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K vs placebo to correct excessive anticoagulation in patients receiving warfarin:
a randomized trial. Ann Intern Med. 2009;150(5):293-300. 22. Crowther MA, Garcia D, Ageno W, et al. Oral vitamin K effectively treats international normalised ratio (INR) values in excess of 10. Thromb Haemost. 2010;104(1):118-121.
Editor's Note
Data for a Common Clinical Dilemma Mitchell H. Katz, MD
A patient receiving warfarin for atrial fibrillation experiences worsening of her chronic obstructive pulmonary disease with purulent sputum. You want to start an antibiotic. Her international normalized ratio (INR) has been rock stable at 2.5. Should you adjust the dose of warfarin? Would the answer Related article page 409 be different if she was just ill and you were not going to use an antibiotic? Does it depend on the antibiotic? This is a common medicine (warfarin) and a common situation (upper respiratory tract infection), and yet there are no easy real-world answers. Harnessing the power of linked medical, pharmacy, and laboratory records and an anticoagulation database, Clark and coauthors show that upper respiratory tract infection increases the risk of excessive anticoagulation even without an-
416
tibiotics, probably because of a combination of eating less, using acetaminophen-containing medications, and developing fever. With antibiotics, the risk increases a bit more, but the difference is not statistically significant. Antibiotics interfering with warfarin metabolism (metronidazole and trimethoprimsulfamethoxazole) were more likely to result in clinically concerning increases in INR (≥5.0). Of importance to us as clinicians is that most patients had minimal changes in the INR with antibiotics, indicating that we should not lower warfarin dosages preemptively. On the other hand, we can take from this study that patients with respiratory tract illness, especially those receiving an antibiotic that interferes with warfarin metabolism, as well as women, patients with cancer, and those with an elevated baseline INR, are at higher risk for excessive anticoagulation and should have additional INR monitoring.
JAMA Internal Medicine March 2014 Volume 174, Number 3
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a GLASGOW UNIVERSITY LIBRARY User on 05/19/2015
jamainternalmedicine.com
Warfarin Interactions With Antibiotics
16. Mahé I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621-1627.
19. Dowd MB, Vavra KA, Witt DM, Delate T, Martinez K. Empiric warfarin dose adjustment with prednisone therapy: a randomized, controlled trial. J Thromb Thrombolysis. 2011;31(4):472-477.
17. Hirsh J, Fuster V, Ansell J, Halperin JL; American Heart Association; American College of Cardiology Foundation. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation. 2003;107(12):1692-1711.
20. Ahmed A, Stephens JC, Kaus CA, Fay WP. Impact of preemptive warfarin dose reduction on anticoagulation after initiation of trimethoprim-sulfamethoxazole or levofloxacin. J Thromb Thrombolysis. 2008;26(1):44-48.
18. Richards RK. Influence of fever upon the action of 3,3methylene bis-(4-hydroxycoumarin) (dicumarol). Science. 1943;97(2518):313-316.
21. Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K vs placebo to correct excessive anticoagulation in patients receiving warfarin:
a randomized trial. Ann Intern Med. 2009;150(5):293-300. 22. Crowther MA, Garcia D, Ageno W, et al. Oral vitamin K effectively treats international normalised ratio (INR) values in excess of 10. Thromb Haemost. 2010;104(1):118-121.
Editor's Note
Data for a Common Clinical Dilemma Mitchell H. Katz, MD
A patient receiving warfarin for atrial fibrillation experiences worsening of her chronic obstructive pulmonary disease with purulent sputum. You want to start an antibiotic. Her international normalized ratio (INR) has been rock stable at 2.5. Should you adjust the dose of warfarin? Would the answer Related article page 409 be different if she was just ill and you were not going to use an antibiotic? Does it depend on the antibiotic? This is a common medicine (warfarin) and a common situation (upper respiratory tract infection), and yet there are no easy real-world answers. Harnessing the power of linked medical, pharmacy, and laboratory records and an anticoagulation database, Clark and coauthors show that upper respiratory tract infection increases the risk of excessive anticoagulation even without an-
416
tibiotics, probably because of a combination of eating less, using acetaminophen-containing medications, and developing fever. With antibiotics, the risk increases a bit more, but the difference is not statistically significant. Antibiotics interfering with warfarin metabolism (metronidazole and trimethoprimsulfamethoxazole) were more likely to result in clinically concerning increases in INR (≥5.0). Of importance to us as clinicians is that most patients had minimal changes in the INR with antibiotics, indicating that we should not lower warfarin dosages preemptively. On the other hand, we can take from this study that patients with respiratory tract illness, especially those receiving an antibiotic that interferes with warfarin metabolism, as well as women, patients with cancer, and those with an elevated baseline INR, are at higher risk for excessive anticoagulation and should have additional INR monitoring.
JAMA Internal Medicine March 2014 Volume 174, Number 3
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a GLASGOW UNIVERSITY LIBRARY User on 05/19/2015
jamainternalmedicine.com
